ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4015G>C (p.Gly1339Arg) (rs876658310)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218595 SCV000278019 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000235377 SCV000293805 uncertain significance not provided 2018-11-23 criteria provided, single submitter clinical testing This variant is denoted APC c.4015G>C at the cDNA level, p.Gly1339Arg (G1339R) at the protein level, and results in the change of a Glycine to an Arginine (GGT>CGT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC Gly1339Arg was not observed in large population cohorts (Lek 2016). This variant is located in beta-catenin down-regulating domain (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Gly1339Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000530639 SCV000647490 uncertain significance Familial adenomatous polyposis 1 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1339 of the APC protein (p.Gly1339Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 233611). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000218595 SCV000686962 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-10 criteria provided, single submitter clinical testing

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